Dimethyl methylphosphonate → 1,1-Dimethylethyl 4-[(1E)-4-(dimethoxyphosphinyl)-3-oxo-1-buten-1-yl]-1-piperidinecarboxylate

HRID 1978366Notes

Reaction equation

HRID 1978366 reaction equation
[CH3:1][P:2](=[O:7])([O:5][CH3:6])[O:3][CH3:4].C([O:10][C:11](/[CH:13]=[CH:14]/[CH:15]1[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17][CH2:16]1)=O)C>O1CCCC1>[CH3:4][O:3][P:2]([CH2:1][C:11](=[O:10])/[CH:13]=[CH:14]/[CH:15]1[CH2:16][CH2:17][N:18]([C:21]([O:23][C:24]([CH3:26])([CH3:25])[CH3:27])=[O:22])[CH2:19][CH2:20]1)([O:5][CH3:6])=[O:7]

Participants

4

Reactant 2

HCID 12958Dimethyl methylphosphonateHCID 17749898tert-Butyl 4-[(1E)-3-ethoxy-3-oxoprop-1-en-1-yl]piperidine-1-carboxylate

Product 1

HCID 1317225781,1-Dimethylethyl 4-[(1E)-4-(dimethoxyphosphinyl)-3-oxo-1-buten-1-yl]-1-piperidinecarboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 13.1 g (106 mM) of dimethyl methylphosphonate in 100 ml of tetrahydrofuran was added 69.2 ml (111 mM) of 1.6M n-butyllithium-hexane dropwise at −78° C. and the mixture was stirred at the prevailing temperature for 10 minutes. To this reaction mixture was added a solution of 14.271 g (50.362 mM) of tert-butyl (E)-4-(2-ethoxycarbonylvinyl)piperidine-1-carboxylate in 100 ml of tetrahydrofuran at −78° C. and the mixture was stirred until the temperature had recovered to room temperature. This reaction mixture was poured in aqueous solution of ammonium chloride and extracted with 3 portions of ethyl acetate. The organic layers were pooled and dried over MgSO4 and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (hexane-ethyl acetate:1/1 to ethyl acetate) to provide the title compound.

Workup

  1. stirringthe mixture was stirred until the temperature
  2. customhad recovered to room temperature
  3. additionThis reaction mixture was poured in aqueous solution of ammonium chloride
  4. extractionextracted with 3 portions of ethyl acetate
  5. dry with materialdried over MgSO4
  6. distillationthe solvent was distilled off under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (hexane-ethyl acetate:1/1 to ethyl acetate)

Sources & evidence

ORD record
ord-77db2964fd9e48c79a9a464d472eb972
Source dataset
uspto-grants-2001_05
Patent number
US06235731B1

Reaction notes

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